Implantable interface device

ABSTRACT

An interface device for implantation in a subject includes a tissue integration layer and a crowning element. The tissue integration layer has a porous structure adapted for ingress of tissue to anchor the device when implanted. The crowning element is adapted for epidermal attachment when the device is implanted and is configured such that once implanted, part of the crowning element extends through the epidermis and is accessible from outside the subject&#39;s body. The porous structure of the tissue integration layer is interconnected for tissue ingress during implantation.

PRIORITY CLAIM

This application is a divisional of, claims the benefit of and priorityto U.S. patent application Ser. No. 15/068,228, filed on Mar. 11, 2016,which claims the benefit of and priority to Australian PatentApplication No. 2015900867 filed on Mar. 11, 2015, the entire contentsof which are each incorporated by reference herein.

FIELD OF THE INVENTION

The present invention relates to implantable devices. It relatesparticularly but not exclusively to devices that are suitable for mediumto long-term implantation within skin or that breach skin to sit withindeeper tissues. Such devices may be used for vascular access, access tobody cavities, coupling of prosthetics, reconstruction of tissue and thelike.

BACKGROUND TO THE INVENTION

Medical implants include devices that are placed within tissue or breachskin to treat, stabilise, remediate, or obviate a range of medicalconditions. The development of biocompatible materials has facilitatedthe design and manufacture of a vast number of devices that are used inthe body or that breach skin, but failure at the interface between thedevice material and the skin and infection of implants are problems thathave proven to be unsolvable.

Implantable devices that breach skin eventually fail and become infecteddue to failure of skin to attach to the devices. This failure ofattachment is consequential to three interrelated pathophysiologicalphenomena: epidermal marsupialisation, whereby epidermis grows under andaround the implant, rather than attaching to it; avulsion, whereby skinpulls away from implant; and infection which complicates and exacerbatesthe other two phenomena. Achieving a marsupialisation-free,avulsion-free, and infection-free interface and method for implantationhas the potential to revolutionise medical practice, permittinglong-term and infection-free access to vascular and body cavities, andfully implantable robotics, prosthetics, and other such devices.

Porosity in skin-implanted devices has been shown to increaseimplantation longevity. However, a permanent, robust and infection-freedesign and method for implantation has proven elusive. A device andmethod for implantation that enables skin attachment would be a quantumimprovement upon what is currently available.

The discussion of the background to the invention included hereinincluding reference to documents, acts, materials, devices, articles andthe like is included to explain the context of the present invention.This is not to be taken as an admission or a suggestion that any of thematerial referred to was published, known or part of the common generalknowledge in Australia or in any other country as at the priority dateof any of the claims.

BRIEF SUMMARY OF THE INVENTION

Viewed from one aspect, the present invention provides an interfacedevice for implantation in a subject, the device including: a tissueintegration layer having a porous structure adapted for ingress oftissue to anchor the device when implanted; and a crowning elementadapted for epidermal attachment when the device is implanted andconfigured such that once implanted, part of the crowning elementextends through the epidermis and is accessible from outside thesubject's body; wherein the porous structure of the tissue integrationlayer is interconnected for tissue ingress during implantation.

Tissue integration into the porous structure of the tissue integrationlayer may be enhanced by application of a negative pressure to thedevice during implantation. In a preferred embodiment, the porousstructure is macroporous and highly interconnected such that it containsvery few or is entirely absent of dead spaces (i.e. non-connectedpores). It is also preferred that the tissue integration layer has acompressive strength sufficient to resist complete compression duringapplication of a negative pressure so as to maintain porosity andcapacity to allow tissue ingress during the implantation phase.

The interface device is formed from one or more biocompatible materials.Such materials may be selected from the group including but not limitedto: a polymer, a metal, a non-metal, a polymer-metal composite, aceramic and combinations including two or more of the foregoing. In someembodiments, the tissue integration layer and the functional element areformed as a unitary piece although it is to be understood that theseparts may be manufactured separately and joined by adhesive, welding,brazing, anchoring or the like.

In some embodiments, one or more of the tissue integration layer, thecrowning element and the device as a whole are at least partiallyflexible. Flexibility permits dynamic integration and movement of thedevice with surrounding tissue during and after implantation.

Preferably, the tissue integration layer contains highly interconnectedpores having diameter of 20 μm to 500 μm to minimise fibroblast deathwithin the pores and collection of cell debris polluting the tissueintegration layer. Dead spaces and cell debris can lead to infection, aswell as limit ongoing tissue integration into the porous structure. Inpreferred embodiments, the pores have a diameter of at least 40 μm.

The crowning element is ideally sized and shaped to optimise epidermalattachment, although the shape may be modified according to theapplication for which the interface device is intended. The shape may beselected from a group including but not limited to toroid, discoid,polygonal, irregular or regular closed shape to name a few.

In some embodiments, the crowning element includes a functionalisedzone. Functionalisation may be aimed at increasing epidermal attachmentand resisting marsupialisation or in the inverse, resisting epidermalattachment to cause directed marsupialisation. The functionalised zonemay be protein optimised e.g. with collagen type 1 or, more desirably,collagen type 4 for enhanced epidermal attachment. The crowning elementmay also include one or more functionalised zones that are optimised forepidermal attachment or epidermal marsupialisation. The functionalisedzones may be provided on the crowning element and may include a junctionbetween the crowning element and the tissue integration layer.

Typically the crowning element is substantially solid and has one ormore channels in functional communication with pores of the tissueintegration layer. The channels permit the transfer of negative pressureapplied during implantation of the device between the crowning elementand the pores of the tissue integration layer.Alternatively/additionally, the crowning element includes fenestrationsto enhance transmission of negative pressure between the crowningelement and the pores of the tissue integration layer. In someembodiments, the crowning element may be completely solid, with negativepressure being applied around it, to the underlying macroporous scaffoldinto which tissue integrates during implantation.

In some embodiments, at least part of the device is biodegradable in thesubject's body. That is, while the product has a stable shelf life, onceimplanted biological processes within the body cause the biodegradablepart of the device to break down and become excreted from the body.

In some embodiments, the crowning element is adapted to be coupled withor receive an accessory device. Once the pores of the tissue integrationlayer are fully or at least substantially filled with tissue, theimplant is securely anchored in vivo and the crowning element can beused to interface with other devices.

In some embodiments, the interface device is required for vascular,tissue, or body cavity access. In such applications, part of the tissueintegration layer is removable to extend a channel in the crowningelement through the scaffold, thereby providing a continuous channel toaccess deeper tissues after implantation. Thus, a through channel in thedevice can provide access to a target vessel, tissues, or cavities. Insome embodiments, the through channel provides a portal for removal offluid from the subject and/or an access point for insertion of aninstrument or other accessory device.

In some embodiments, the crowning element is configured to couple withor receive an accessory device such as a trocar, tube, drain,prosthetic, electronic device, robotic device, catheter, ostomy device,drug delivery device, a fixation device, or tissue building scaffold, toname a few. In some embodiments, the crowning element may includemagnetic or electronic material to aid coupling with an accessorydevice.

In some embodiments, the device includes a plurality of crowningelements configured to extend through the epidermis when implantedproviding a plurality of access points that are accessible outside thesubject's body, with a single tissue integration layer providing ananchor when implanted.

Viewed from another aspect, the present invention provides a method forimplanting an interface device for transcutaneous access in a subject,the method comprising the steps of: preparing tissue at an implant siteof the subject; placing the interface device, having a porous(preferably macroporous) tissue integration layer and a crowning elementat the prepared implant site, with the porous tissue integration layerin contact with the prepared tissue; and applying negative pressure tothe device to enhance tissue integration into the pores of the tissueintegration layer.

Preferably, preparing the tissue site includes de-epithelializing anarea of skin at the implant site; and excising or incising a section ofdermis sufficient to accommodate the tissue integration layer. Suchsteps are ideally performed using known techniques that maintain asterile environment for implantation of the interface device.

Preferably, the implantation method further includes applying a dressingover the device and the implant site so as to substantially seal off thedevice and implant site wherein negative pressure is applied through thedressing. In effect, the negative pressure suitable dressing provideshermetic coverage.

The negative pressure can be applied at between negative 25 mmHg andnegative 500 mmHg, but is ideally applied at approximately negative 125mmHg, and is applied for between 1 and 28 days.

In some embodiments, the negative pressure is applied continuously overthe implantation period. However, it is to be understood that thenegative pressure may be applied for much shorter periods (hours todays), periodically, in bursts or at quasi-random intervals over thecourse of 1 to 28 days to enhance tissue ingress into the pores of thetissue integration layer. In some embodiments, cycling the pressurebetween “on” and “off” or “on” and a reduced pressure condition may bepreferred.

In some embodiments where a through channel across the device isrequired for access to deeper tissues, the method includes removing partof the tissue integration layer to provide a through channel across thedevice for accessing deeper tissues. The removed part of the tissueintegration layer may be with or without ingressed tissue. Removal maybe by e.g. boring, reaming, drilling, surgical excision, use of acutting trocar, or twisting of a trocar built into the through channel.Alternatively, a sharp-tipped instrument or object could be pushedthrough the tissue integration layer to form a through channel withoutthe need to remove a core of the tissue integration layer first.

In some embodiments, the method includes coupling an accessory device tothe crowning element, or inserting an accessory device into the crowningelement. This can occur at any stage during implantation or afterimplantation. In some embodiments, use of the implanted device mayinvolve periodically coupling and decoupling an accessory device, suchas a peritoneal dialysis catheter. In other embodiments, an accessorydevice may be permanently coupled. In other embodiments still, noaccessory device may be coupled to the interface device.

In some embodiments, the device may be implanted into a first tissuesite and then grafted to a different tissue site which may be in thesame subject (donor subject), or in a different subject (donee subject).Thus, the method may further include the steps of: after tissue hasintegrated into the porous structure, excising the implanted device fromthe implant site; preparing tissue at a recipient site; and placing theexcised implanted device at the prepared recipient site.

Viewed from yet another aspect of the present invention, there isprovided an implant device for implantation in a human or animalsubject, the implant device including: a tissue integration layer havinga porous structure for ingress of stabilising tissue to anchor thedevice when implanted; and a crowning element adapted for epidermalattachment when the device is implanted; wherein the porous structure ofthe tissue integration layer is configured to enhance tissue ingressduring implantation of the device.

The crowning element may include a functionalised zone that is optimisedfor epidermal attachment.

Preferably, the porous structure of the tissue integration layer ismacroporous and with highly interconnected pores to enhance tissueingress during implantation particularly when negative pressure isapplied. The stabilising tissue may include one or more of dermal andsubcutaneous tissue and optionally, the tissue integration layer mayhave a surface with one or more functionalized zones that are optimisedfor epidermal attachment. Optimisation may be with protein e.g.collagen, particularly collagen type 4. Alternatively/additionally, thecrowning element may have one or more functionalized zones that areoptimised for epidermal attachment.

It is to be understood that the device may be configured forimplantation or grafting wholly or partly internally of the subject'sbody, or transdermally. The device may be implanted in any type ofstabilising tissue such as dermal tissue, subcutaneous tissue, bone,fat, breast, cartilage, organs, fascia, muscle and blood vessel walls.In embodiments where the stabilising tissue is beneath skin, the devicemay be implanted using an open surgical technique or, in someembodiments, using a minimally invasive or natural orifice insertiontechnique. Ideally, the porous structure of the tissue integration layeris configured to enhance tissue ingress during implantation, preferablyduring application of negative pressure. Other features of the implantdevice may be incorporated, including those that are described inrelation to the aforementioned interface device.

Viewed from yet another aspect, the present invention provides a kitincluding: a piece of macroporous tissue integrating material; and oneor more crowning elements attachable to the tissue integrating material;wherein the one or more crowning elements are affixable to themacroporous tissue integrating material to form an implantable interfacedevice for use in a human or animal subject.

The one or more crowning elements may be adapted for epidermalattachment when the device is implanted, and may include one or morefunctionalised zones that are optimised for epidermal attachment orepidermal marsupialisation.

In some embodiments, the kit includes one or more of an adhesive, abonding agent and one or more anchors for affixing one or more crowningelements to the tissue integrating material. The kit may also includeone or more dressings and tubing for connecting the interface devicewith a source of negative pressure during implantation.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will now be described in greater detail withreference to the accompanying drawings. It is to be understood that theembodiments shown are examples only and are not to be taken as limitingthe scope of the invention as defined in the claims appended hereto.

FIG. 1A is a schematic illustration of an interface device according toan embodiment of the invention, shown in cross section.

FIG. 1B is a top schematic illustration of a crowning element 120 withsurface optimised zones.

FIG. 2 is a schematic illustration of an interface device according toanother embodiment of the invention, also shown in cross section.

FIG. 3 is a schematic illustration of the interface device of FIG. 2coupled with an accessory device in the form of a trocar.

FIG. 4 is a schematic illustration showing an implant site prepared forimplantation of a device according to an embodiment of the invention.

FIG. 5 is a schematic illustration showing the prepared implant sitefrom FIG. 4, with the device implanted as in FIG. 1A and covered by adressing with negative pressure applied according to an embodiment ofthe invention.

FIG. 6 is a schematic illustration of the interface device used with anaccessory device according to another embodiment of the invention andused with a bone fixation screw.

FIG. 7 is a schematic illustration of the interface device that is amodification of the device illustrated in FIG. 5 and used with a similaraccessory device.

FIG. 8A is a schematic illustration of an implanted device excised fromthe implant site with integrated tissue and ready for grafting toanother site.

FIG. 8B is a schematic illustration showing the excised device from FIG.8A grafted to a recipient site.

FIG. 9 is a schematic illustration of a kit according to an embodimentof the invention.

FIG. 10 is a schematic illustration showing implantation of an interfacedevice in the aortic wall, according to an embodiment of the invention.

FIG. 11 is a schematic illustration showing use of embodiments of theinvention for interfacing with a subject's abdominal wall to performperitoneal dialysis.

FIG. 12 shows results from the inventor's experiments demonstratingenhanced stability of collagen type 1 after covalent bonding to abiomaterial.

FIG. 13 shows results from the inventor's experiments demonstratingenhanced stability of collagen type 4 after covalent bonding to abiomaterial.

DETAILED DESCRIPTION OF THE INVENTION

Various embodiments and features of the invention are discussed hereinby reference to the drawings which are not to scale and are intendedmerely to assist with explanation of the invention. Referring firstly toFIG. 1A, there is shown an interface device 100 for implantation in asubject. In particular, the implant device 100 is shown implanted in asubject's skin, specifically the epidermis 220, dermis 230, andsubcutaneous tissue 240.

The device includes a tissue integration layer 110 that has amacroporous structure adapted for ingress of dermal tissue 230 andsubcutaneous tissue 240 to anchor the device in place when implanted.The interface device 100 also includes a crowning element 120 which isadapted for location, in the example shown, in at least the epidermis220 although the thickness of the crowning element may also necessitateplacement at least in part in the dermis 230 as shown. Placement of atleast part of the crowning element 120 in the epidermis 220 enablesepidermal attachment to the crowning element such that part of thecrowning element extends through the epidermis when implanted so that itis accessible from outside the subject's body. The porous structure ofthe tissue integration layer 110 is interconnected for tissue ingressduring implantation. This may be enhanced by application of negativepressure to the device during implantation.

Ideally, the tissue integration layer 110 is 25-90% of the thickness ofthe dermis 230 and is arranged on subcutaneous tissue 240 forimplantation. In some embodiments, it is preferable for the tissueintegration layer 110 to be thicker or thinner, as may be necessitatedby the clinical application for which it is used. Moreover, the tissueintegration layer 110 may be placed at a variety of depths within theskin and in some embodiments, may span a number of tissue layersincluding tissue layers deeper than the skin and subcutaneous tissue240. Various arrangements of the tissue integration layer relative tothe crowning element 120, and various implantation locations in the skinare contemplated within the ambit of the present invention and, ideallywith application of negative-pressure, achieve tissue integration intothe porous material of the tissue integration layer 110 with epidermalattachment, to the crowning element 120 and/or aspects of the tissueintegration layer surrounding the crowning element.

The tissue integration layer 110 has a highly interconnected macroporousstructure such that the number of dead spaces (i.e. non-connected pores)are minimised or, in a preferred embodiment, entirely absent. Themacroporous structure of tissue integration layer 110 provides ascaffold into which dermal and subcutaneous tissue may integrate,particularly during application during of negative pressure across theinterface device 100 during the implantation stage. In a preferredembodiment, the tissue integration layer 110 has such highinterconnectivity between pores that it imitates the structure ofcancellous (i.e. trabeculated) bone. Such a structure has highinterconnectivity as discussed above, as well as structural strengthwhich can withstand the compressive forces applied to the tissueintegration layer 110 during application of a negative pressure. In someembodiments, the tissue integration layer 110 may be optimised withantibacterial, cell growth stimulating and other agents that enhancetissue ingress and anchoring of the device in vivo. Once implanted, thetissue integration layer 110 provides a foundation for the crowningelement 120 and any accessory devices that may pass through or beattached to it.

In some embodiments, it may be desirable for all or part of the implantdevice 100 to be flexible. Flexibility allows dynamic integration andmovement of the device 100 with dermis 230 and subcutaneous tissue 240.Human tissue is flexible and dynamic. It may be advantageous for theimplant device 100 to be flexible and dynamic to move synchronously withtissue, thereby minimising shear forces at the interface between theepidermis 220 and the crowning element 120.

Ideally, the pore size in the tissue integration layer 110 issufficiently large to preclude or minimise the likelihood of fibroblastsdying from hypoxia and lack of nutrients. Cell death is known to resultin the pores filling with cell debris that in turn can lead to infectionand failure of the device. A pore diameter of between 20 μm and 500 μmis acceptable. Ideally, however, a pore size of no smaller than 40 μmdiameter is desirable. Additionally, there should be a negligible numberof dead spaces, the pores should be highly interconnected, and thereshould be few acute angles in the pores. Acute angles, where the porenarrows down to less than 40 μm diameter, may predispose to cell death.Pore size, shape, and interconnectivity in the tissue integration layer110 are optimised to permit tissue ingress particularly duringapplication of negative pressure and also after the negative pressurehas been removed. Effective integration of tissue into the tissueintegration layer 110 anchors and protects the overlying epidermis 220from avulsion forces. Advantageously, the application of negativepressure minimises or removes avulsion forces, which protects theepidermis 220 and thereby stabilises the device 100.

The tissue integration layer 110 and crowning element 120 may be formedof a single unitary piece of biocompatible material. Alternatively, thecrowning element 120 may be formed separately from the tissueintegration layer 110 and bonded, welded, brazed, fused or otherwisejoined to form a single interface device 100 before or afterimplantation in the subject. In some embodiments, the device 100 orparts of it are manufactured using 3D printing or computer controlledmaterial deposition. Depending on its size and/or application, thetissue integration layer 110 may comprise a number of repeating volumesof macroporous scaffold material although in some embodiments it may bedesirable for a computer controlled 3D printer or material depositingapparatus to manufacture a randomised or substantially randomisedstructure. The shape of the scaffold of the tissue integration layer 110can be highly variable. In some embodiments it is desirable that theshape of the tissue integration layer 110 represents the subject's“usual” anatomy at the site of implantation. For example, the site ofimplantation may include the subject's jaw or nose in circumstanceswhere the natural anatomical structure has been removed due to illnessor was never formed, and the tissue integration layer is shaped toprovide such structure. The crowning element 120, once implanted,provides a site for attachment of devices or insertion of devices andinstruments to deeper tissues or organs.

Suitable materials for the interface device may include polymers andco-polymers, metals, non-metals and polymer-metal composites or acombination of these materials. One such combination with demonstratedsuitability is the mixed macrodiol polyurethane co-polymer Elast-Eon™,as a toric shaped crowning element, melt-bonded to an underlyingtantalum macroporous scaffold.

The crowning element 120 is ideally sized and shaped to optimiseepidermal attachment to its surface. The shape may be e.g. toroid,discoid, polygonal or any other irregular or regular closed shape. Theshape of the crowning element 120 may be determined according to theintended function of the interface device 100. For instance, aninterface device 100 intended to couple with a single existing accessorydevice such as a catheter, drainage tube or perfusion line a particularthrough channel profile may be desirable. Generally, the channel 122extends at least through a central portion of the crowning element 120and as such, a toroid or discoid shape would be appropriate.

In other applications, e.g. where several access points are required (asmay be required to anchor a prosthetic or robotic device to a limb), theshape of the crowning element 120 may be modified, enlarged or contouredto suit the accessory device and the body part to which it is beingcoupled. In some applications, the perimeter of the crowning element 120may be regular, somewhat regular, or irregular.Alternatively/additionally, in some applications, there may be two ormore crowning elements 120 on the tissue integration layer 110 providingtwo or more locations at which the interface device 100 extends throughthe epidermis 220 facilitating access to deeper tissues from outside thesubject's body. Examples are provided in FIGS. 6 and 7.

Where no channel 122 is required, (e.g. for attachment of a prosthetic)negative pressure can be applied around the crowning element 120 toenhance tissue ingress into the macroporous structure of the tissueintegration layer 110. In some embodiments, the crowning element 120 mayhave pores, micro-channels perforations or fenestrations to enhancedistribution of the negative pressure through and between the crowningelement and to the tissue integration layer 110 during implantation,thereby enhancing or encouraging tissue ingress into the pores of thetissue integration layer 110.

During implantation, tissue integration between the device 100, dermis230, and subcutaneous tissue 240 begins around the outer surfaces of thetissue integration layer 110 and works toward the centre region of thecrowning element 120 including channel 122 (where present). Pores in thetissue integration layer 110 that are close to subcutaneous tissue 240experience subcutaneous tissue integration to a greater extent thanpores in the tissue integration layer that are closer to the epidermis220 and to some extent the dermis. Once the tissue integration layer isintegrated into the dermis 230 and subcutaneous tissue 240, close tissueapposition to the scaffold structure provides a foundation and anchorfor overlying epidermis. Once the device is implanted, part of thecrowning element 120 protrudes through the epidermis 220 so that it isaccessible from outside the subject's body.

A particular advantage arising from the structure of the interfacedevice 100 disclosed herein is that it permits the transmission ofnegative pressure to the underlying tissue so that tissue integrationinto the porous structure of the tissue integration layer 110 anchorsthe device, while concurrently allowing attachment of the epidermis 220to the crowning element 120 or upper tissue integration layer. Thisadvantage has not hitherto been seen in implant devices or devicesintended to interface with skin.

In some embodiments, the crowning element 120 includes one or more zonesthat have been functionalised with chemical functional groups tooptimise epidermal 220 attachment to the crowning element 120. In someembodiments, the functionalised zone is protein optimised e.g. withcollagen. It is known that cellular attachment to protein-optimisedsurfaces is faster and more robust than is the case for non-optimisedsurfaces.

Surface optimisation may involve a range of techniques for bondingchemical or biologically active molecules to the surface of the crowningelement 120 to modify the extent to which epidermal attachment occurs.In one embodiment, glow discharge plasmas are used to createfunctionalised zones on the surface of the crowning element 120. Thefunctionalised surface can then bind biologically active molecules suchas proteins. Although any generic form of functionalisation may besuitable, Acetaldehyde plasma polymerisation (Aapp) has been determinedby the inventor to be suitable for achieving surface functionalisationof the crowning element 120 for epidermal attachment.

In published prior art, implants have been surfaced-optimised withcollagen type 1. The inventor has undertaken research to assess thestability of collagen type 4 against collagen type 1 and discoveredthat, after incubation with 8M urea, collagen type 4 had much greaterstability than collagen type 1. Results are shown in FIGS. 12 and 13 foradsorbed and covalently bound collagen (using Aapp) for collagen types 1and 4 respectively. FIG. 12 shows that after less than one day, collagentype 1 was completely eluted from the specimens to which collagen type 1was adsorbed, while 92% was retained on specimens that were Aappfunctionalised (covalently bound). In contrast, the results in FIG. 13show that adsorbed collagen type 4 was eluted to approximately 59% ofits initial concentration after 20 days while surprisingly, covalentlybound collagen type 4 showed no evidence of elution over the same periodthus exhibiting starkly improved stability. Thus, the inventor hasobserved that covalent bonding significantly improved resistance todegradation and peeling-off of collagen type 4 from the testedbiomaterial.

These results led the inventor to hypothesise that use of collagen type4 in vivo will increase the longevity of implants. Accordingly, surfaceoptimisation of the crowning element 120 with collagen type 4 is likelyto enhance epidermal attachment to the crowning element. However,optimisation with collagen type 4 is not requisite for epidermalattachment to the crowning element 120. The surface of the tissueintegration layer 110 and/or its junction with the crowning element 120may also be optimised with collagen type 4 to stabilise the implant 100and increase its longevity. For example, a coating of collagen type 4may be applied to the surface of the tissue integration layer 110.

The entire surface of the crowning element 120 may be optimised.Alternatively, as shown in FIG. 1B, surface optimisation may be confinedto specific functional zones or applied in a pattern configured toachieve a functional outcome. For example, in areas of the crowningelement 120 where it is desirable to enhance epidermal attachment, thefunctionalised zone 126 may be optimised with protein such as collagentype 4. Alternatively/additionally, in areas of the crowning element 120where it is desirable for there to be no or minimal epidermalattachment, the functionalised zone 124 may be inert. Optionally, anarea of the crowning element 120, such as zone 124 may be functionalisedor treated with an agent to mitigate infection or other biologicalprocesses. In some applications epidermal attachment to the uppersurface of the tissue integration layer 110 (but no deeper) is desirableto create a skin-biomaterial interface. In that case, the entirecrowning element 120 may be changed to resist epidermal attachment sothat epidermal marsupialisation alongside the crowning element mayoccur.

It is to be understood that the surface optimisation of the crowningelement 120 is controllable and may therefore be restricted to discretefunctionalised zones. Discrete functionalised zones may be achieved byclose control of the plasma polymer coating process or other methods ofsurface functionalisation. Alternatively/additionally, areas notrequiring surface treatment may be masked prior to subjecting thecrowning element 120 to the optimisation process. Alternatively, theentire crowning element 120 may be optimised and the areas that do notrequire surface optimisation may be treated or covered to deactivate orobstruct active molecules outside the required functionalised zones.

Surface optimisation of the crowning element 120 may also occur throughphysical modification of the surface. For example, the entire surface orspecific functionalised zones may be nanotextured, e.g. to eitherenhance or minimise epidermal attachment as may be desired (not shown).Additionally/alternatively, surface optimisation of the crowning element120 may involve a combination of physical and chemical modificationtechniques. Ideally, surface optimisation is provided on a desired area(functionalised zone) of the crowning element. Such an area may includepart or all of the junction between the crowning element 120 andscaffold of the tissue integration layer 110. Where minimal or noepidermal attachment is desired, the crowning element 120 may include aninert functionalised zone 124 that promotes epidermal marsupialisation.Alternatively, where epidermal attachment is desired, the crowningelement 120 may include a functionalised zone 126 which acts to guideand promote epidermal attachment.

In some embodiments, the crowning element 120 is shaped for couplingwith or insertion of an accessory device or to provide a particularfunction such as drainage or fixation. Such an embodiment is illustratedin FIG. 2. Here, the crowning element 120 is shaped as a tube having anouter body portion 120A and an inner body portion 120B. A channel 122formed through the crowning element 120 is in functional communicationwith pores of the tissue integration layer 110 via channels or pores 128to facilitate tissue integration during implantation. Additionally, theinner portion 120B of the crowning element continues the hollow channelfrom outer body portion 120A forming a “through channel” 130 whichpermits transcutaneous access to deeper tissues.

FIG. 3 shows an accessory device 300, in the form of a trocar, insertedinto deeper tissues via the through channel 130. Transcutaneous accessvia a trocar may be useful for introduction of catheters, tubes,miniaturised cameras and a variety of other instruments used to treat,inspect or manipulate deeper tissues.

A range of implantation devices may incorporate the interfacingtechnology described herein, such as e.g. bone anchored rods, bonescrews, tubes and the like. In such arrangements, the functional rod,screw, tube or the like is incorporated into or replaces the inner bodyportion of the crowning element 120 which extends into the deepertissue. These devices can use a similar method of implantation as forthe interface device 100 shown in FIG. 1A.

FIG. 4 shows a tissue implant site 400 which has been prepared forimplantation of an interface device 100 according to an embodiment ofthe invention. An area of skin at the implant site 400 isde-epithelialized and a section of the dermis 230 and epidermis 220 isremoved revealing subcutaneous tissue 240. In some embodiments, somesubcutaneous tissue 240 may also be removed although this need not bethe case to achieve effective tissue integration when the device 100 isimplanted. Removal of a section of skin as shown creates a space at theimplant site 400 that is sufficient to accommodate the tissueintegration layer 110 of the interface device 100. It is to beunderstood that while FIG. 4 shows removal of a substantially circularsection of dermis 230, the removed tissue section and hence the spacecreated for the interface 100 may take any suitable shape. For example,the tissue integration layer may be square, round, oblong or have athree dimensional shape achieved by contoured excision of the dermis.

In some embodiments, it may be desirable to remove a larger area of thedermis 230 than the epidermis 220. This accommodates an interface device100 as shown in FIGS. 1A to 3 with a crowning element 120 having asmaller diameter than the tissue integration layer 110 to which it isattached. In other embodiments involving smaller implant devices 100,preparing the tissue implant site 400 may involve forming a simpleincision and inserting the device like a button into a button hole. Inother cases still, larger area of skin is de-epithelialized and asmaller area of the dermis 230 below (and optionally subcutaneous tissue240) is excised. The larger area of tissue is removed from the dermis230 to accommodate the larger tissue integration layer 110 of the device100. Tissue elasticity permits insertion of the interface device 100when the size of the tissue integration layer 110 exceeds the size ofthe opening in the epidermis 220 and/or dermis 230. However, forsimplicity, it may be desirable to remove a section of tissue having asomewhat regular shape.

FIG. 5 shows the interface device 100 in cross section placed in aprepared implant site 400. A foam layer 610 is applied over the implantdevice 100. Plastic sheeting 620 is applied over the foam layer 610(although the foam layer may, in some cases be substituted with gauze orother dressing material or omitted altogether). The plastic sheeting 620forms a seal over the implant site 400 and a negative pressure isapplied, through the dressing 620, via a tube 630. Application of anegative pressure increases vascularisation, improves tissue healing andgranulation, and removes exudate and chemical mediators of inflammation,thereby enhancing tissue ingress into the pores of tissue integrationlayer 110.

The negative pressure may be generated by any suitable source such as avacuum pump or the like. Ideally, the negative pressure source isconfigurable to apply a pressure between negative 25 mmHg and negative500 mmHg over a pre-definable duration. Typically, the pressure appliedduring implantation is in the range of negative 125 mmHg+/−100 mmHgalthough pressures as low as negative 500 mmHg may be desirable in someapplications.

Negative pressure may be applied continuously, intermittently orcyclically over a duration sufficient to achieve tissue integration intothe pores of tissue integration layer 110. In most embodiments theduration is in the range of 1 to 28 days. Typically, a shorter durationof 1 to 15 or even 1 to 10 days is sufficient and in many applications,a duration of 6 to 7 days is sufficient to achieve adequate tissueintegration although a duration as short as 2 to 6 days or even 2 to 3days may be sufficient. In some cases, application of negative pressurefor one day or for a few (e.g. 3 to 6) hours is sufficient. In mostapplications, cyclic application of negative pressures achieves tissueintegration more effectively. For example, the desired negative pressuremay be applied for a period of ten minutes followed by a period of no(or reduced magnitude) negative pressure for a period of two minutes,with the cycle repeated for the duration of tissue integration. Oncetissue integration is complete, the negative pressure is disconnected,the dressing 620 and foam layer 610 are removed together with the tubing630 and the interface device 100 remains in vivo.

Owing to the unique structure of the interface device 100, during theperiod of tissue ingress into the tissue integration layer 110,epidermal cells concurrently migrate over the tissue integration layerand adhere to the crowning element 120 (or upper aspects of the tissueintegration layer if the crowning element is altered to resist epidermalattachment) such that, upon removal of the plastic sheeting 620, aportion of crowning element 120 (or the entire crowning element)protrudes through the epidermis 220. Upon removal of the plasticsheeting 620, foam 610 and tubing 630, the interface device 100 isanchored within dermal and subcutaneous tissue.

In some embodiments, it may be desirable to remove part of the tissueintegration layer 110 in order to extend the crowning element channel122 and provide a through channel 130 across the device for accessingdeeper tissues, e.g. as shown in the embodiments shown in FIGS. 2 and 3.Removal of a “core” of the tissue integration layer 110 may be achievedusing a drill, reamer or by puncturing the tissue integration layerusing a sharp tipped device such as a trocar, needle or the like. Insome embodiments, it may be desirable to remove the excised section oftissue integration layer 110 from the body. In other embodiments, thetissue integration layer 110 is partly or completely biodegradable.

In some embodiments, a channel formed through the implanted device 100may require occlusion to close the interface access to deeper tissues.In such applications, a permanent or removable/reusable cap may beinserted through or applied over the channel 122 as required.

The size of the interface device 100 may be determined according to theclinical application for which the interface device is required. Adiameter as small as 0.5 or 1 cm is sufficient to support long-termintegration of the device in the dermis 230. Similarly, the shape of thedevice may be determined according to the clinical application.Embodiments illustrated herein show a circular and substantially toricdevice with a channel 122 extending though the thickness of the crowningelement 120. As described above, in some embodiments, the channel 122may be extended, through the tissue integration layer 110 to provide athrough channel 130 for accessing deeper tissues of the subject. It isto be understood, however, that the tissue integration layer 110 mayhave any size or shape. In some embodiments, the tissue integrationlayer 110 has a generic shape and is configured or trimmed to therequired size just prior to implantation.

In some embodiments, the interface device 100 is supplied as a unitarypiece with the tissue integration layer 110 and the crowning element 120pre-attached. In other embodiments, the implant device 100 is providedin a kit 900 (FIG. 9) containing a generic macroporous tissueintegration layer 110 and one or more crowning elements 120. An adhesiveor bonding agent 910, anchors or other fixation devices for attachingone or more crowning elements 120 to the tissue integration layer 110may also be provided in the kit. Ideally, one or more foam layers 610and adhesive plastic sheets 620 are also provided in the kit togetherwith tubing 630 (not shown) for connecting the interface device, oncecovered by the dressing with a negative pressure pump (not shown).

When the interface device 100 is provided in kit form, a clinician cantrim the generic macroporous tissue integration layer 110 to the desiredsize and shape, and apply one or more crowning elements 120 to thetissue integration layer 110 at locations that are determined for aspecific clinical application. The interface device 100 may be assembledby attaching one or more crowning elements 120 to the tissue integrationlayer 110 before it is implanted, or the tissue integration layer may beplaced first, and a crowning element 120 attached to the tissueintegration layer at the implant site.

FIG. 6 shows interface devices 100 used with an accessory device 300 inthe form of bone screws 310, 312, plate 330 and external fixation screws320, 322. In this embodiment, an interface device 100 is used at thepoint of transcutaneous entry for each of the bone screws 310, 312 intothe subject's body. In one embodiment, the interface device 100 isimplanted in accordance with a method described in relation to FIGS. 4and 5 prior to inserting the bone screws 310, 312. Once there iseffective tissue integration, a bone screw 310 is inserted throughchannel 122 in the crowning element 120 in one of the implanted devices100 and the threaded shaft 314 is screwed through the tissue integrationlayer 110 so that the screw penetrates the entire depth of the interfacedevice 100 and accesses the deeper tissues. The bone screw 310 is thenadvanced toward and into the bone 700, where the threaded shaft 314engages the bone to achieve fixation. The process is repeated withsecond bone screw 312. An external fixation plate 330 is then attachedto stabilise the bone screws 312, 314 using external fixation screws320, 322.

In another approach, the bone screws 310, 312 may be assembled with aninterface device 100 ex-vivo. That is, prior to implantation of thedevice, a bone screw 310 is inserted into the channel 122 in thecrowning element 120 and the threaded shaft 314 is screwed through thetissue integration layer 110 so that the bone screw 310 rotates freelyinside a through channel 130 that it forms through the full thickness ofthe interface device 100. In a single procedure, a layer of the dermisis removed to create an implant site 400 as described above, and theinterface device is implanted using the method discussed above with thebone screw 310 extending therethrough. The bone screw 310 is thenadvanced into the deeper tissues, toward and into the bone 700 where thethreaded shaft 314 is screwed into the bone. Foam layer 610 and plasticsheeting 620 are then applied over and/or around the external portion ofthe bone screw 310 forming a seal, and negative pressure is applied toencourage ingress of tissue into the pores of the tissue integrationlayer 110 through which the bone screw 310 extends.

FIG. 7 shows a similar embodiment to FIG. 6, with a bone screw 310inserted through a first interface device 100A and into bone 700 with anexternal portion of the bone screw 310 attached to an external fixationplate 330 by external fixation screw 320. Additionally, a secondinterface device 100B is provided, through which two bone screws 312,214 have been inserted. Bone screws 312, 214 are also attached to theexternal fixation plate 330 by external fixation screws 322, 324. Inthis embodiment, the interface device 100B has two crowning elements120A, 120B which extend through the epidermis 220 at differentlocations, though both are commonly anchored in the dermis 230 by asingle tissue integration layer 110A. Advantageously, the common tissueintegration layer 110A provides an additional stabilising anchor forbone screws 312, 314. Either implantation method described with respectto the embodiment shown in FIG. 6 may be used for implantation of one orboth of the interface devices 100, 100A shown in FIG. 7.

In some clinical applications an implanted interface device may berequired for permanent implantation e.g. in the case of prosthetics. Inother applications, the interface device may be required to remain invivo for an extended period of weeks, months or even years and may beexplanted from the patient when no longer required. In some embodiments,the tissue integration layer is biodegradable in the biologicalenvironment leaving only the crowning element 120 in the epidermis 220and dermal tissue 230 for removal. For example, in a patient receivingchemotherapy, it may be desirable for the tissue integration layer tobiodegrade after the completion of chemotherapy, leading to spontaneousextrusion of the crowning element. Alternatively, depending on the sizeof the interface device, explanation may be a simple procedure performedwith local anesthetic and requiring few or no stiches. In other caseswhere the interface device is larger, a skin graft or flap may berequired.

In some cases, such as in FIGS. 6 and 7 after effective bone fixation isachieved, the accessory device, in this case the bone screws 310, 312,314, may be removed. The interface devices 100, 100A can remain in vivo,with a cap or plug closing the channel 122. Advantageously, if the bonefixation subsequently fails, the cap can be removed and the interfacedevice 100, 100A re-used for infection free access to the bone.Alternatively, the implant device can be explanted or removed asdescribed above.

The principles illustrated in the bone fixation examples of FIGS. 6 and7 can be applied in a range of clinical applications requiring safe,infection free, long term transdermal attachment of a device or accessto deeper tissues, body cavities or blood vessels. It is to beunderstood, however, that embodiments of the inventive interface devicemay be used entirely internally in any situation involving epithelium orendothelium and deeper tissue, e.g. to provide an interface across ablood vessel, the gut, bladder, pleural cavity or the like. An exampleis shown in FIG. 10, where an interface device 100 is implanted in thewall of the aorta 930. Here, tissues of the aortic wall 830 ingress intothe tissue integration layer 110 during implantation, while the crowningelement 120 acts as an attachment point for luminal endothelium 820, all(ideally) with the assistance of negative pressure. This device can beused to provide trans-aortic access to the abdomen 910 and surroundingtissues.

In other embodiments, the interface device 100 may provide a tissueintegration layer 110 adapted for integration of a number of differenttissue types. Thus, in addition to the tissue structures involved withskin integration such as adipocytes, fibroblasts, and collagen, ingressof other cell types such as myoblasts and osteoblasts may be seen withintegration into muscle and bone. Alternatively/additionally, thecrowning element 120 may extend through the tissue integration layer 110as in FIGS. 2 and 3, to perform a particular function in the deepertissue. By way of example, an inner body portion 120B of the crowningelement 120 may terminate in or provide a thread, hook or anchor forengaging bone, cartilage or other tissue.

FIG. 8A is a schematic illustration of a section of excised tissue 260into which an interface device 100 has been implanted according toembodiments of the invention. There is full tissue integration at thedermis 230 and epidermal attachment to the crowning element 120 suchthat only a small portion extends through the epidermis 220 tofacilitate external access. Typically, the section of excised tissue 260is elliptical and is trimmed to remove triangular end portions 262 priorto grafting. The excised tissue 260 contains a safe margin of tissue andcan be grafted elsewhere on the subject. FIG. 8B shows the trimmedexcised tissue 270 containing the implanted interface device 100 graftedinto a site that has been prepared in the same way as the implant site400 in FIG. 4, with the section of dermis 230 that has been removed fromthe recipient site prepared to receive the shape of the trimmed excisedtissue 270.

Advantageously, tissue integration has already occurred in the interfacedevice 100 in explanted tissue 260. Accordingly, grafting requires nonegative pressure and enables the interface device to be utilised inregions of the body (including internally) where application of aplastic sheeting 620 and negative pressure is challenging orimpractical. Sutures 272 or a sterile dressing (not shown) over therecipient site 270 may be all that is required for tissue healing,thereby providing safe, infection free, long term attachment of aninterface device for access to deeper tissues, body cavities or bloodvessels.

Once implanted, the interface device 100 provides a mechanism fortranscutaneous access to deeper tissues including underlying bloodvessels and body cavities. This access may be directly through a channel122 in the interface device 100 or via a tube or other accessory device300 inserted through the channel 122 or functionality built into thetissue integration layer 110 or an inner body portion of the crowningelement 120. Alternatively/additionally, the implanted interface device100 provides an attachment site for other biomaterials and devices. Inother embodiments still, the implanted device 100 provides for extendedvascular access, peritoneal cavity access, pleural cavity access,bladder access, organ access, or airway access. Such access may permitdelivery of medications, fluids, nutrition, gas (e.g. air via atracheostomy tube) or drainage of fluid (e.g. urine from the bladder orpleural fluid from the pleural cavity).

As described herein, the accessory device 300 may include a trocar,tube, drain, prosthetic, electronic device, robotic device, catheter,ostomy device, drug delivery device, fixation device, and tissuebuilding scaffold to name a few. In such devices 300, negative pressurecan be delivered to deeper tissues via the fenestrations in the crowningelement 120 or via the lumen of the trocar, tube, drain, catheter orostomy device. In some embodiments, implanted device 100 may also allowlater introduction, integration and attachment of a trocar, tube, drain,catheter or ostomy device.

Recent improvements in the area of peritoneal dialysis include newdialysis solutions, better delivery tubes, and cyclers for automatedperitoneal dialysis. Notwithstanding these advances displacement, cuffextrusion, leakage, and infection remain problematic. Infection of theperitoneal dialysis catheter at the skin interface is a particularconcern. Catheter-related infections can lead to cellulitis, necrotisingfasciitis, and peritonitis. Advantageously, long-term and safe access tothe peritoneal cavity can also be achieved using the inventive interfacedevice.

FIG. 11 is a schematic illustration showing an embodiment of theinvention for accessing the peritoneal cavity 260 to perform dialysis.Here, interface device 100 has been implanted for transcutaneous accessas described previously. In use, a polymer dialysis tube 360 is passedthrough the implant device 100, crosses the abdominal wall 250 andenters the peritoneal cavity 260 where dialysate is delivered throughholes 390 in the dialysis tube. A deep cuff 380 (known in the art)placed in the abdominal wall 250 stabilises the dialysis tube 360internally. The embodiment illustrated in FIG. 11 shows the throughchannel in crowning element 120 and tissue integration layer 110oriented at an angle that permits the dialysis tube 360 to restcomfortably along the subject's abdomen.

The implanted device 100 can enable long-term access to the gut, bodyorgans, and the central nervous system. For example, embodiments of theinventive interface device are suitable for achieving drainage of theurinary tract (kidneys, ureters, or bladder). In other embodimentsstill, the implanted device 100 may itself, be extended into or formpart of a prosthetic device.

In some cases, the inventive device may be used in the reconstruction ofsurgical, traumatic or congenital tissue defects. For example, followingresection of a cancer involving the mandible, a tissue integration layer110 could be shaped (using 3D printing, moulds, trimming or othertechniques) to bridge the bone gap and/or subcutaneous tissue and dermisgap. A crowning element 120 attached to the tissue integration layer 110could be used to bridge the skin gap. Tissue integration would beassisted by application of a negative pressure as described elsewhereherein.

In yet other cases, the inventive device may be used to form a roboticprosthetic limb. The crowning element 120 forms the “prosthetic” or actsas an attachment point for the prosthetic device, while the tissueintegration layer and crowning element work together to form a longterm, infection free interface with skin.

Where the terms “comprise”, “comprises”, “comprised” or “comprising” areused in this specification (including the claims) they are to beinterpreted as specifying the presence of the stated features, integers,steps or components, but not precluding the presence of one or moreother features, integers, steps or components or group thereof.

It is to be understood that various modifications, additions and/oralterations may be made to the parts previously described withoutdeparting from the ambit of the present invention as defined in theclaims appended hereto.

It is to be understood that the following claims are provided by way ofexample only, and are not intended to limit the scope of what may beclaimed in future. Features may be added to or omitted from the claimsat a later date so as to further define or re-define the invention orinventions.

What is claimed is:
 1. A method for implanting an interface device fortranscutaneous access in a subject, the method comprising the steps of:a. preparing tissue at an implant site of the subject; b. placing theinterface device, having a porous tissue integration layer and acrowning element, at the prepared implant site, with the porous tissueintegration layer in contact with the prepared tissue, the interfacedevice including: i. a tissue integration layer having a porousstructure forming a scaffold into which tissue integrates to anchor thedevice when implanted, ii. a crowning element attached to an uppersurface of the tissue integration layer and configured such that onceimplanted, there is epidermal attachment to part of the crowningelement, and part of the crowning element extends though the epidermisand is accessible from outside the body, and iii. a removable sealcapable of applying a negative pressure overlaying the part of thecrowning element accessible from outside the subject's body, wherein theporous structure of tissue integration layer is interconnected fortissue ingress during implantation, and wherein the tissue integrationlayer is sized and shaped to provide a foundation that supports thecrowning element such that when implanted, the tissue integration layeris entirely anchored beneath the epidermis; and c. applying negativepressure to the device to enhance tissue integration into the pores ofthe tissue integration layer.
 2. The method according to claim 1,wherein preparing the tissue site includes: a. de-epithelializing anarea of skin at the implant site; and b. excising or incising a sectionof dermis sufficient to accommodate the tissue integration layer.
 3. Themethod according to claim 1, wherein the method includes applying adressing over the device and the implant site so as to substantiallyseal off the device and implant site, wherein negative pressure isapplied through the dressing.
 4. The method according to claim 1,wherein the method includes removing part of the tissue integrationlayer to provide a through channel across the device for accessingdeeper tissues.
 5. The method according to claim 4, including the stepof puncturing the tissue integration layer using a sharp tipped deviceto access deeper tissues.
 6. The method according to claim 1, whereinthe method includes coupling an accessory device to the crowningelement.
 7. The method according to claim 1, wherein the negativepressure is between negative 25 mmHg and negative 500 mmHg.
 8. Themethod according to claim 1, wherein the negative pressure is appliedfor between 1 and 28 days.
 9. The method according to claim 1, whereinthe negative pressure is applied intermittently.
 10. The methodaccording to claim 1, further including the steps of: a. after tissuehas integrated into the porous structure, excising the implanted devicefrom the implant site; b. preparing tissue at a recipient site; and c.placing the excised implanted device at the prepared recipient site,wherein the implant site and the recipient site are in the same subject.